Drugs, which show cholesterol lowering effects through a mechanism of inhibiting the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase), are generally called “statin”. Among them, the first generation compounds, developed earliest, include simvastatin, lovastatin, pravastatin and the like, which are fermentation products, and the second generation compounds, which are synthetic drugs, include atorvastatin, fluvastatin, rosuvastatin, pitavastatin and the like.
Among them, atorvastatin is a very promising compound, which showed the highest growth rate during the recent three years and had a market size of 13.2 billion dollars in the year 2006. Also, the annual average growth rate was more than 20%.
International Patent Publication No. WO 89/07598, assigned to Warner-Lambert Company commercially producing atorvastatin, discloses a process for the preparation of atorvastatin. In this patent, as can be seen in the following reaction scheme (1), a 1,4-dione compound represented by formula A is allowed to react with a chiral intermediate represented by formula B, to obtain a compound represented by formula C, which is then converted to atorvastatin:

In the reaction scheme 1, the first reaction comprises refluxing the compound of formula A and the compound of formula B in a hydrocarbon solvent, such as toluene, cyclohexane or a mixture thereof, and allowing the resulting compound of formula C into contact with aqueous acid solution such as aqueous hydrochloric acid solution.
However, the preparation process according to the reaction scheme 1 has problems in that the reaction time in the first reaction is very long (about 100 hours), leading to an increase in side reactions, and the total yield of the product is as very low as about 15%, because it is not easy to remove produced byproducts.
International Patent Publication No. WO 02/057274 discloses a process for preparing atorvastatin, in which, as shown in the following reaction scheme 2, a compound of formula (A) and a compound of formula (D) are allowed to reflux and condensate by using acetic acid in a xylene solvent to prepare a compound of formula (E), which is then hydrolyzed, thus preparing atorvastatin.

However, in the preparation process according to the reaction scheme 2, the reaction time is very long (about 44 hours) and, in addition, intensive reaction conditions are required, because the reaction must be carried out at high temperature (not less than 110° C.) using xylene, having a high boiling point, as a reaction solvent. Also, it is difficult to remove the remaining solvent, the toxicity of the solvent itself can cause a serious problem in terms of the safety of workers, and thus it is unsuitable to apply the preparation process in actual industrial fields. In addition, there are problems in that the production of byproducts increases due to a very long reaction time and that it is not easy to remove byproducts.
International Patent Publication No. WO 04/106299 discloses a process for preparing atorvastatin, in which, as shown in the following reaction scheme 3, a compound of formula F and a compound of formula B are allowed to reflux and condensate by using pivalic acid in a mixed solvent of heptane, toluene and tetrahydrofuran.

However, in the preparation process according to the reaction scheme 3, the reaction time is very long (22-25 hours), a high reaction temperature is required, leading to an increase in side reactions, and a separation and purification process is carried out using column chromatography in order to remove produced byproducts, leading to a decrease in the yield of the reaction. Thus, it is not suitable to apply the preparation process in actual industrial fields.
International Patent Publication No. WO 05/012246 discloses a process for preparing atorvastatin, in which, as shown in the following reaction scheme 4, a compound of formula H and a compound of formula I are allowed to reflux in a tetrahydrofuran solvent, and the reaction product is separated and purified using column chromatography:

Unlike the 1,4-dione compound disclosed in International Patent Publication No. WO 89/07598, the 1,4-dione compound of formula H shown in the reaction scheme 4 has a structure very similar to a 1,4-dione compound, which is used in the present invention. However, similarly to the preparation process disclosed in International Patent Publication No. WO 89/07598, the preparation process according to the reaction scheme 4 is difficult to apply in actual industrial fields, because the reaction time is very long (about 2 days) and, in addition, the yield of the product is as very low as about 19%.
Also, preparation processes, disclosed in U.S. Pat. Nos. 4,647,576 and 4,681,893, have problems in that optically pure products cannot be produced and, even though the products can be separated into pure products, the separation and purification process is very expensive. In addition, there are problems in that the reaction time is long, and not less than 50% of the starting material is lost, leading to a decrease in the yield of the reaction.
The reason for the results (long reaction time and low yield) of the prior preparation processes as described above is that a substituent group (e.g., an amide or ester compound) is present at carbon location 3 of the reactant 1,4-dione compound (formula A, F or H), and thus, during the reaction, a structural arrangement resulting from the steric hindrance of carbon locations 2 and 3 in the molecule of the 1,4-dione compound inhibits a cyclization reaction with the chiral intermediate (formula B, D or I), resulting in a decrease in the total reaction yield (J. Med. Chem., 1991, 34, 357˜366).